Characterization of the acetylcholine-reducing effect of the amyloid-beta peptide in mouse SN56 cells.
We previously reported that the amyloid-beta protein (Abeta) reduces the synthesis of acetylcholine (ACh) in a mouse septal cell line, SN56, without causing death of the cells. Here, we report that the ACh-reducing effect of either Abeta 1-28 or Abeta 1-42 (100 nM; 48 h) in SN56 cells can be prevented by a co-treatment with the tyrosine kinase inhibitors, genistein (75 microM) and tyrphostin A25 (50 microM). Treatment of the cells with either of these inhibitors alone increased ACh levels. An enhancement of the cellular ACh content was also obtained with aphidicolin, a compound which inhibits DNA synthesis. However, co-treatment of the cells for 48 h with aphidicolin (500 nM) and Abeta 1-42 (100 nM) did not prevent the reduction in ACh levels caused by the peptide. Furthermore, this effect could not prevented by a pre-treatment with vitamin E (50 microg/ml). These results suggest that the ACh-reducing effect of Abeta in SN56 cells is dependent on tyrosine phosphorylation, but is not dependent on DNA synthesis and may not be mediated by free radicals.
Pedersen
W A
WA
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, MA 02118, USA.
Blusztajn
J K
JK
D000109:Acetylcholine / Q000096:biosynthesis*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016590:Aphidicolin / Q000008:administration & dosage / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020032:Tyrphostins; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D009570:Nitriles; D010446:Peptide Fragments; D020032:Tyrphostins; C084358:amyloid beta-protein (1-28); C079836:tyrphostin 25; D014810:Vitamin E; D016590:Aphidicolin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000109:Acetylcholine